Exceptional and Durable Responses to TDM-1 After Trastuzumab Failure for Breast Cancer Skin Metastases: Potential Implications of an Immunological Sanctuary

Breast Cancer (BC) skin metastases represent a challenging clinical scenario. Although they usually arise when other distant metastases are already present, they may also represent a form of locoregional recurrence (LRR). Systemic therapy in this setting may have a role both in case a radical locoregional approach is unfeasible in order to achieve disease control, and as adjuvant strategy after radical removal of cutaneous lesions, in order to prevent or delay subsequent disease spread. Systemic therapy for HER2+ metastatic BC (MBC) currently relies on anti-HER2 targeted agents. In this context TDM1 is an option in trastuzumab-resistant patients.Here we present 2 cases of isolated skin metastases in patients with HER2+ BC progressing during or early after trastuzumab-based therapy, showing impressive responses to TDM1. We hypothesize that the unique properties of skin immune microenvironment may explain the failure of trastuzumab, which exerts its action also through immunological mechanisms, and the subsequent outlier responses to TDM1, that relies on a partially different mechanism of action

Quantum Return Probability for Substitution Potentials

We propose an effective exponent ruling the algebraic decay of the average quantum return probability for discrete Schrodinger operators. We compute it for some non-periodic substitution potentials with different degrees of randomness, and do not find a complete qualitative agreement with the spectral type of the substitution sequences themselves, i.e., more random the sequence smaller such exponent.Comment: Latex, 13 pages, 6 figures; to be published in Journal of Physics

Quantum Diffusion in Separable d-Dimensional Quasiperiodic Tilings

We study the electronic transport in quasiperiodic separable tight-binding models in one, two, and three dimensions. First, we investigate a one-dimensional quasiperiodic chain, in which the atoms are coupled by weak and strong bonds aligned according to the Fibonacci chain. The associated d-dimensional quasiperiodic tilings are constructed from the product of d such chains, which yields either the square/cubic Fibonacci tiling or the labyrinth tiling. We study the scaling behavior of the mean square displacement and the return probability of wave packets with respect to time. We also discuss results of renormalization group approaches and lower bounds for the scaling exponent of the width of the wave packet.Comment: 6 pages, 4 figures, conference proceedings Aperiodic 2012 (Cairns

Autologous micrografts and methotrexate in plantar erosive lichen planus: healing and pain control. A case report

Erosive lichen planus is an uncommon variant of lichen planus. We report a case of long-standing and refractory plantar ELPs causing disabling and opiate-resistant pain treated with 'classic' meshed skin graft combined with RigeneraVR micrografts. After approximately 9 months follow-up, no clinical recurrence or pain were observed. Erosive lichen planus (ELP) is an uncommon variant of lichen planus, involving oral cavity and genitalia and, less often plantar areas, where it usually presents with chronic erosions of the soles, along with intense, disabling pain and progressive loss of toenails. An abnormal immune cellular response (CD8+ lymphocytes and macrophages) and the consequent altered production of multiple mediators (interleukin-12, interferon-gamma, tumor necrosis factor-alpha, RANTES and MMP-9), seem to play a crucial role in the pathogenesis, although the etiology remains uncertain. From a histological point of view, ELP shows keratinocyte apoptosis, intense inflammatory response and basal epithelial keratinocytes TNF-alpha overexpression. Several therapies have been proposed, with variable and controversial results. While topical corticosteroids and topical calcineurin inhibitors are the treatments of choice for localized forms, short pulses of systemic glucocorticoids, phototherapy, and systemic immunosuppressants are recommended for generalized cases. Surgery has been reported as a possible therapeutic option in refractory and stable cases with localized lesions, either alone or with cyclosporine. Herein, we report a case of longstanding and refractory plantar ELPS causing disabling and opiate-resistant pain treated with 'classic' meshed skin graft combined with RigeneraVR micrografts

Drug-Related Cardiotoxicity for the Treatment of Haematological Malignancies in Elderly.

Meyer Paul Hugo. Diderot oder die Ambivalenz der Aufklärung, Neumann, 1987. In: Recherches sur Diderot et sur l'Encyclopédie, n°4, 1988. pp. 164-165

Field Theory Approach to Quantum Interference in Chaotic Systems

We consider the spectral correlations of clean globally hyperbolic (chaotic) quantum systems. Field theoretical methods are applied to compute quantum corrections to the leading (`diagonal') contribution to the spectral form factor. Far-reaching structural parallels, as well as a number of differences, to recent semiclassical approaches to the problem are discussed.Comment: 18 pages, 4 figures, revised version, accepted for publication in J. Phys A (Math. Gen.

Induction chemotherapy followed by alternating chemo-radiotherapy in stage IV undifferentiated nasopharyngeal carcinoma

In locally advanced undifferentiated nasopharyngeal carcinoma (UNPC), concomitant chemo-radiotherapy is the only strategy that gave better results over radiation alone in a phase III trial. Adding effective chemotherapy to a concomitant chemo-radiotherapy programme may be a way to improve the results further. 30 patients with previously untreated T4 and/or N2–3 undifferentiated nasopharyngeal carcinoma were consecutively enrolled and initially treated with 3 courses of epidoxorubicin, 90 mg/m2, day 1 and cisplatin, 40 mg/m2, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/m2/day, days 1–4 and fluorouracil, 200 mg/m2/day, days 1–4, i.v. bolus, (weeks 1, 4, 7) alternated to 3 courses of radiation (week 2–3, 5–6, 8–9–10), with a single daily fractionation, up to 70 Gy. WHO histology was type 2 in 30% and type 3 in 70% of the patients. 57% had T4 and 77% N2–3 disease. All the patients are evaluable for toxicity and response. All but one received 3 courses of induction chemotherapy. Toxicity was mild to moderate in any case. At the end of the induction phase 10% of CRs, 83.3% of PRs and 6.7% of SD were recorded. All the patients but one had the planned number of chemotherapy courses in the alternating phase and all received the planned radiation dose. One patient out of 3 developed grade III–IV mucositis. Haematological toxicity was generally mild to moderate. At the final response evaluation 86.7% of CRs and 13.3% of PRs were observed. At a median follow-up of 31 months, 13.3% of patients had a loco-regional progression and 20% developed distant metastases. The 3-year actuarial progression-free survival and overall survival rates were 64% and 83%. Induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients' compliance optimal. This approach showed a very promising activity on locally advanced UNPC and merits to be investigated in phase III studies. © 2000 Cancer Research Campaign http://www.bjcancer.co

oncological outcome of fat grafting for breast reconstruction after cancer

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